Changes in fatty acid levels (saturated, monounsaturated and polyunsaturated) during pregnancy

A good nutritional status of fatty acids (FA) during pregnancy is important for the mother’s health in order to meet the needs of foetal growth and development. Studies evaluating the effects of FA deficiency states during pregnancy have mainly focused on polyunsaturated fatty acids (PUFA). In particular, a maternal deficiency of omega-3 polyunsaturated fatty acids (n-3 PUFA) may affect placental angiogenesis and vasculogenesis, thereby affecting foetal development (brain, muscle, eye, motor nerve and adiposity) [1]. It is known that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are two of the most important FA for the cognitive and visual development of the foetus [2‐5]. Maternal fatty acid status is also crucial in late pregnancy because this is when the human foetal brain grows rapidly and high amounts of DHA accumulates in it [1, 5]. Thus, the foetus during the third trimester is especially vulnerable to developmental deficits due to a poor status of n-3 PUFA, and this could cause problems in neurological development [6, 7]. However, few studies have assessed the changes in FA during pregnancy [8‐10]. An appropriate balance with n-3 and omega-6 polyunsaturated fatty acids (n-6 PUFA) is necessary [11, 12] because a high concentration of maternal arachidonic acid (AA) has been associated with deleterious outcomes, such as major depression in the mother [13, 14], or preterm delivery [15]. However, a higher maternal AA/DHA ratio at delivery and heterozygosity for the FADS1 genetic variant have shown positive long-term effects on processing speed in children at 9 years of age [7].

Therefore, an adequate fatty acid profile in early and late pregnancy is crucial for the health of both the mother and the child. To our knowledge there is a dearth of literature on the changes in plasma FA concentrations throughout pregnancy. A recent systematic review analysed how the n-3 and n-6 PUFA profile is modified during pregnancy [16]. It included only three studies [17‐19] and showed that DHA and n-6 PUFA concentrations increase throughout pregnancy, while EPA remains unchanged. Similar findings were obtained in research conducted with a Canadian pregnant population with and without gestational diabetes [20]. Saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) have been studied less [17, 19, 21]. The survey by Pinto et al. [17] of 225 pregnant Brazilian women found an increase in SFA and MUFA concentrations throughout pregnancy. Taking into account the importance of FA status for maternal and foetal health, a better understanding and knowledge of this subject would help obstetrics and health professionals to identify possible abnormal values and decide whether treatment is necessary and which treatment to recommend. The aim of the current study is therefore to analyse the changes in maternal fatty acid concentrations (saturated, monounsaturated and polyunsaturated) during pregnancy in a cohort of pregnant women from a Mediterranean country in Europe.

This longitudinal study describes the changes in FA during pregnancy in a larger sample of women than in previous studies and, to our knowledge, for the first time in a population from the Mediterranean area. It provides valuable data on a wide range of FA, these being total SFA and lauric acid, myristic acid, palmitic acid and stearic acid; total MUFA and palmitoleic acid and oleic acid; total n-6 PUFA and linoleic acid, dihomo-γ-linolenic acid and AA; n-3 PUFA and EPA and total DHA. The data on these FA were determined using high-quality methods and evaluated at two moments of gestation (first and third trimester). This has made it possible to describe changes to the different types of FA during pregnancy. The concentrations of SFA, MUFA and PUFA n-6 increased from the first to the third trimester of gestation, except for AA, the concentrations of which decrease. In contrast, n-3 PUFA and EPA concentrations decreased during pregnancy, while DHA concentrations remained stable. It appears that essential fatty acids DHA and AA, which have a preferential placental transfer to the foetus, do not evolve in the same way as other FA during pregnancy.

There are few research projects that have analysed SFA and MUFA serum concentrations throughout pregnancy, conducted with Brazilian and Dutch pregnant woman [17‐19, 21]. Our results are consistent with their findings, as they also found an increase in SFA and MUFA during pregnancy. This increase could be due to an increase in biosynthesis to cover requirements, since the rise in serum concentration may not be related to the small variation in the mothers’ dietary intake [30, 31], as our research group found in this sample of healthy pregnant women in relation to their intake during pregnancy [32]. The SFA may play a key role in supporting foetal membrane growth, as the SFA bio-magnification process could help to satisfy AA demands in foetal circulation and DHA in the brain [33]. However, the crucial role played by SFA has yet to be determined. An adequate concentration of MUFA is also fundamental during pregnancy because a non-optimal level has been associated with a high risk of preterm delivery and low weight at birth [33]. Oleic acid concentration could be a biomarker for a lack of essential fatty acid in the mother’s diet, as has been shown in animal models [33]. In addition, it has been suggested that the consumption of monounsaturated fats could benefit DHA metabolism because they have a low amount of LA and thus do not interfere with endogenous conversion of α-linolenic acid (ALA) to DHA [34]. Further research is needed to analyse their role during pregnancy.

In terms of PUFA, we found that n-6 PUFA concentrations increased during gestation, whereas essential fatty acid (EPA, DHA, AA) concentrations decreased or remained stable. Our results are partially in concordance with the literature. For instance, Zhao et al. [20] observed that Canadian pregnant women without diabetes showed higher serum concentrations of all fatty acids except EPA at 35–37 weeks of pregnancy than at 24–28 weeks. A systematic review found that levels of absolute concentrations of DHA increased and EPA did not change [16]. Pinto et al. [17], in a study involving Brazilian pregnant women, showed that from the first to second trimesters the serum FA concentrations, EPA + DHA, increased greatly, but a slight increase in DHA and a decrease in EPA (although not statistically significant) were observed in the third trimester. However, our study found no significant variation in DHA from the first to third trimesters and observed a significant decrease of around 15% in EPA concentrations. It may be that the DHA synthesis from EPA was more efficient than from ALA [35, 36] and that DHA concentrations could be regulated by a different biosynthesis or mobilization mechanism [35‐38]. In fact, n-6 and n-3 PUFA families compete for metabolism by desaturation enzymes, and therefore a Western or industrialized diet rich in vegetable oils that are high in LA would inhibit the synthesis of n-3 PUFA by ALA. In addition, AA is an essential fatty acid that is preferential for transfer to the foetus along with DHA [1]. Our findings show that AA concentrations also decrease by around 8% during pregnancy. Although LA serum concentrations increased, it does not appear that it was to be converted into AA, which may suggest that enzymatic activity of delta 5 desaturase could be reduced. Other researchers have suggested that LA may compete with other fatty acids, including AA, for acylation [39, 40]. In agreement with our results, Stewart et al. [38] found no differences in the AA concentrations of erythrocytes; however, other researchers have found an increase in AA serum concentrations during pregnancy [16, 17, 20]. The reasons for the different findings are unclear. It should be noted that the systematic review by Wilson et al. [16] included only three studies that assessed serum concentrations of FA, one from Brazil and two from the Netherlands, whose populations have different dietary patterns with a high level of heterogeneity between them. It is possible that the differences could be due to when the measurements were taken, to sample size, the fatty acid assay protocol or the study populations. More research is needed to clarify how essential fatty acids change over the course of the entire pregnancy.

Furthermore, our study is a secondary analysis of a clinical trial of iron supplementation. In this sense, a physiological relationship between iron and fatty acids is hypostatized since, for instance, ferritin may incorporate FA in its structure in addition to iron [41, 42]. However, our results did not show that the iron dosage of the supplementation had any effect on FA concentration.

To our knowledge this is the first study of the changes in maternal serum FA during pregnancy in a Mediterranean region. According our findings, circulating FA – specifically SFA, MUFA and n-6 PUFA – increases throughout pregnancy. This could be explained by a synthesis mechanism or mobilization of the maternal fat store, since the concentrations may not be related to dietary intake. Given this situation, we could consider that the increase in SFA, MUFA and n-6 PUFA serum concentration during pregnancy seems to indicate that the metabolic mechanisms involved may offer an optimal nutritional availability to meet the increased demands of these FA due to the increased growth and development of the foetus at the end of gestation. Nevertheless, essential fatty acid concentrations, which are preferential for transfer to the placenta, may be more complexly regulated. During early pregnancy the PUFA derived from the diet are stored in maternal adipose tissue. Indeed, n-3 PUFA serum concentration has been related to food consumption in pregnant woman [8, 10, 17, 27] insofar as it is transferred from intake to maternal fat stores. The amount of n-3 PUFA stored in the maternal adipose tissue could vary depending on the habitual dietary intake of n-3 fatty acids. However, metabolic and physiological changes occur during pregnancy, and these involve the complex synchronization of maternal, placental and foetal fat metabolism to ensure a continuous supply of n-3 and n-6 PUFA to the foetus [35]. Some mechanisms could be related to the mobilization of maternal fat stores, an increase in the elongation and desaturation of FA regulated by oestrogen, the differential placental uptake of FA or the rate of DHA conversion synchronized according to the period of maximal foetal demand [35‐38]. The transfer of n-3 and n-6 PUFA to the foetus increases from 20 weeks of gestation and reaches a peak in the last trimester of pregnancy with a high maternal transfer of DHA and AA to ensure foetal demand [1, 35]. Overall, this decrease or non-modification of essential fatty acids during pregnancy, closely related to their intake, indicates that there are specific physiological mechanisms, such as preferential FA transfer between mother and foetus, so as to ensure high foetal demands are met [35]. This might put the mother at risk of deficiency when her intake is insufficient. Indeed, it has been found that low n-3 PUFA status and imbalance between n-6 and n-3 PUFA in early pregnancy increase the risk of postpartum depression after delivery [10, 14]. This could lead us to consider that the mechanisms involved in its storage in maternal fat, together with other possible complex mechanisms of metabolic synchronization of maternal, placental and foetal fat could be insufficient to guarantee the FA needs in situations of low contributions. In general, for all FA, further testing of normal FA levels during pregnancy would be necessary for better evaluations and follow-ups. In addition, more research is needed on the metabolic mechanisms of FA during pregnancy.

Given that essential fatty acid concentrations and their balance depend on both biological mechanisms and dietary supply, an optimal dietary intake is needed to ensure proper functioning of biological mechanisms so as to facilitate correct foetal growth and development. For this reason, we believe that the pregnancy control reviews carried out by obstetricians and health professionals should include dietary advice on foods rich in these FA, verify consumption of these foods and thus FA, and determine the serum concentrations of essential FA. There is some evidence that supports the benefits of an adequate intake of FA. Fish and seafood consumption during pregnancy has been reported to be beneficial for offspring neurocognitive development [43, 44]. Several other research projects have associated an inadequate balance of n-3 and n-6 PUFA profiles during pregnancy with deleterious consequences for the child, such as neurodevelopment disorder [43, 6], immune system disease [45, 46] and cardiometabolic risk and adiposity [47, 48]. In addition, AA is a precursor of prostaglandin and other metabolites, which play a key role in the late pregnancy period and delivery [49]. Nevertheless, an excessive activation of inflammatory mediators during pregnancy might lead to deleterious effects, such as gestational diabetes, preeclampsia or pre-term delivery [15].

The main strength of our study is its longitudinal design, which enabled us to analyse variations in serum FA concentrations throughout pregnancy. Another strength is the bigger sample size compared to other research [17‐21]. However, several limitations should be considered. Although the sample is of voluntary pregnant women from a randomized clinical trial with a control group, the sample avoids the selective survival error by selecting women from each area of the primary health care ASSIR service specific for pregnant women, from an entire region. This provided a good representation of the socioeconomic and educational levels of the sample, among other aspects. In addition, exhaustive inclusion and exclusion criteria were fulfilled, previously designed and agreed on with the ASSIR service, thus guaranteeing a sample of healthy pregnant adult women. Incentives were given to minimize the loss of women in the pregnancy follow-up, consisting of follow-up visits interspersed with study visits, economic incentives for midwives who carried out these visits, and informational incentives for mothers about their health status and that of their baby. In the design phase of the study, all procedures, masking and quality control were systematized and monitored by a group external to the research group. Nevertheless, our findings may not be extended to all populations as ethnicity, nutritional habits and lifestyle may impact on the fatty acid levels. In the assessment of FA, it was not possible to assess ALA, one of the main n-3 PUFA, in our sample. Furthermore, due to the lack of reference values, our study was unable to apply a cut-off value regarding the percentage of the pregnant population that is above or below the optimal level. Therefore, our findings indicate that it is necessary to establish reference values according to the variation of FA in each trimester. Moreover, taking into account that our results show a decrease in essential fatty acids at the end of pregnancy due to the demands of the foetus, health and nutrition counselling provided by obstetricians and health professionals could add that mothers consume foods rich in FA from the beginning of the pregnancy to prevent levels from dropping excessively at the end of gestation. In addition, clinical guidelines during pregnancy could include the assessment of FA in each trimester, so that professionals could identify those women who are at risk and recommend specific treatment or advice if necessary.

In conclusion, the circulating serum concentration of SFA, MUFA and n-6 PUFA increases during pregnancy, whereas essential fatty acids such as AA and EPA decrease and DHA remains unchanged. Therefore, the increase in SFA, MUFA and n-6 PUFA serum concentration during pregnancy, which is related to specific metabolic mechanisms during pregnancy, seems to offer an adequate availability of these FA for increased foetal growth and development at the end of pregnancy. However, the decrease or non-increase in essential fatty acids during pregnancy may indicate that there are specific physiological mechanisms that might put the mother at risk of deficiency when her intake is insufficient. More research is necessary to analyse the role of FA during pregnancy.